Abstract Title

Synthesis and Testing of New MTN Inhibitors as Novel Antibiotics

Disciplines

Chemicals and Drugs | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry

Abstract

In the last decade, a new epidemic of antibiotic resistant microbes has swept the globe. With few new FDA approved antibiotics in the past 20 years, there is a need for new and novel antibiotics to treat drug resistant microbes. Methylthioadenosine nucleosidase (MTN) an important metabolic enzyme for microbes that is absent from humans. Drugs that inhibit MTN, while not inhibiting mammalian Methylthioadenosine phosphorylase (MTAP), could be valuable new antibiotics. In this study, potential inhibitors identified by in silico screening were tested for anti-MTN activity. Several urea-base compounds with tighter binding to MTN than MTAP were found. In addition, a urea-based analog was synthesized and fully characterized showing correct structure and activity against E. coli MTN.

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Synthesis and Testing of New MTN Inhibitors as Novel Antibiotics

In the last decade, a new epidemic of antibiotic resistant microbes has swept the globe. With few new FDA approved antibiotics in the past 20 years, there is a need for new and novel antibiotics to treat drug resistant microbes. Methylthioadenosine nucleosidase (MTN) an important metabolic enzyme for microbes that is absent from humans. Drugs that inhibit MTN, while not inhibiting mammalian Methylthioadenosine phosphorylase (MTAP), could be valuable new antibiotics. In this study, potential inhibitors identified by in silico screening were tested for anti-MTN activity. Several urea-base compounds with tighter binding to MTN than MTAP were found. In addition, a urea-based analog was synthesized and fully characterized showing correct structure and activity against E. coli MTN.